摘要
背景:基因电转染是一种很有前景的治疗方法。瘤内的基因电转染有已达到抗肿瘤治疗的临床评价的范围。越来越多的研究表明,抗肿瘤的有效性不仅取决于转染的效率,而且取决于免疫应答的诱导和血管的效应,导致细胞死亡的非特异性诱导。实时无创的光学成像方法可使这些动态的生物过程的纵向研究得以实行。目的:在本研究中,用一种非侵入性的生物发光技术来进一步探索有关的实时监测基因电转染到肿瘤的转染效率以及治疗后细胞死亡的现象。方法:应用转基因的发光肿瘤,观察肿瘤的生长,自死亡的细胞停止发光以后,接着观察治疗的有效性或肿瘤坏死区域的出现。同时评价了皮下肿瘤报告基因的转染效率(iRFP蛋白和荧光素酶)。结果:我们的研究结果表明,报告基因的转染能够导致非特异性抗肿瘤的有效性,甚至肿瘤的完全消失。使用发光的肿瘤,我们还能够间接地设想之前描述的电穿孔的血管效应。此外,采用荧光素酶编码质粒的瘤内基因电转染,我们定位了表达的源主要在肿瘤周围而不在肿瘤局部。结论:根据获得的数据我们提出了与基因转染到肿瘤相关的一些现象的新的见解,应在设计更好的和更有效的癌症基因治疗方案时引起重视,以加快技术转化为临床试验。
关键词: 电穿孔,基因转染,生物发光,肿瘤,荧光性,转染,在体成像
Current Gene Therapy
Title:Visualization of Nonspecific Antitumor Effectiveness and Vascular Effects of Gene Electro-Transfer to Tumors
Volume: 16 Issue: 2
Author(s): Urska Kamensek, Marie-Pierre Rols, Maja Cemazar, Muriel Golzio
Affiliation:
关键词: 电穿孔,基因转染,生物发光,肿瘤,荧光性,转染,在体成像
摘要: Background: Gene Electro Transfer (GET) is a promising method for therapeutic purposes. Intratumoral GET has reached clinical evaluation for antitumor treatment. An increasing number of studies suggests that antitumor effectiveness not only depends on the transfection efficiency, but also on the induction of immune responses and vascular effects that result in the nonspecific induction of cell death. Real time noninvasive optical imaging methods allow longitudinal studies of these dynamic biological processes. Objective: In the present study, a noninvasive bioluminescence technology was used to further explore the phenomena associated with GET to tumors by a real time monitoring of the transfection efficiency as well as cell death following the treatment. Method: By using transgenic light-producing tumors, tumor growth was visualized, and since dead cells stop producing light, effectiveness of the treatment or the emergence of necrotic areas in the tumors was followed visually. The transfection efficiency of reporter genes (iRFP protein and luciferase) in the subcutaneous tumors was also evaluated. Results: Our results showed that the GET of a reporter gene can lead to nonspecific antitumor effectiveness and even complete regression of tumors. Using light-producing tumors, we were also able to indirectly visualize the previously described vascular effects of electroporation. Additionally, using the intratumoral GET of a luciferase encoding plasmid, we localized the source of the expression mainly in the peritumoral and not in the tumoral region. Conclusion: The data obtained provide new insights into some of the phenomena associated with GET to tumors, which should be taken into account when designing improved and more effective cancer gene therapy, in order to accelerate the transfer of the technology into clinical trials.
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Urska Kamensek, Marie-Pierre Rols, Maja Cemazar, Muriel Golzio , Visualization of Nonspecific Antitumor Effectiveness and Vascular Effects of Gene Electro-Transfer to Tumors, Current Gene Therapy 2016; 16 (2) . https://dx.doi.org/10.2174/1566523216666160331125611
DOI https://dx.doi.org/10.2174/1566523216666160331125611 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
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